尼非韦罗微乳热敏凝胶对小型猪阴道黏膜炎症刺激性的研究

发布时间：2018-02-28 03:24

本文关键词： 小型猪尼非韦罗微乳热敏凝胶炎症　出处：《中国新药杂志》2017年19期 　论文类型：期刊论文

【摘要】：目的:研究尼非韦罗微乳热敏凝胶(NFVR/ME-TISG)对小型猪阴道黏膜的炎症刺激性。方法:将9只雌性小型猪随机分为基质凝胶组、NFVR/ME-TISG组(25 mg·d~(-1))和壬苯醇醚-9(N-9)凝胶组(25 mg·d~(-1))。肌注苯甲酸雌二醇后12 d,开始阴道给药5 m L·d~(-1),连续7 d,给药前和末次给药后24与72 h,收集阴道灌洗液(cervicovaginal lavages,CVL),流式细胞仪检测CVL中的中性粒细胞,末次给药后72 h收集阴道组织,苏木素伊红染色法(hematoxylineosin,HE)评价小型猪阴道黏膜组织溃疡、坏死、细胞浸润、出血、充血、水肿等指标,免疫组织化学法(immuno-histochemical,IHC)检测阴道黏膜组织中CD_(45)~+表达的分布。结果:与基质凝胶组相比,N-9凝胶组CVL中炎性细胞的中性粒细胞数目明显增加(P0.01),阴道黏膜出现上皮局部脱落、炎性细胞增多、出血和水肿,CD_(45)~+累积光密度(integrated optical density,IOD)值(33.95±6.69)显著增高(P0.05);而NFVR/ME-TISG组未见明显变化。结论:NFVR/ME-TISG未明显引起小型猪阴道黏膜的炎症刺激性,安全性较好,有望作为阴道外用杀微生物剂候选物进一步研发。
[Abstract]:Objective: to study the inflammatory irritation of NFVRME-TISG on vaginal mucosa of miniature pigs. Methods: nine female miniature pigs were randomly divided into two groups: NFVRP / ME-TISG group (25 mg 路dan-1) and nonphenylether group (9N-9) gel group. 12 days after estradiol acid, 5 mL 路d ~ (-1) of estradiol was administered by vagina for 7 days, 24 and 72 hours after the last administration. The vaginal lavage fluid was collected and the neutrophils in CVL were detected by flow cytometry. Vaginal tissue was collected 72 hours after the last administration. Hematoxylineosin HEH was used to evaluate the indexes of mucosal ulcer, necrosis, cell infiltration, hemorrhage, hyperemia, edema and so on. Immunohistochemical method was used to detect the expression of CD45 ~ + in vaginal mucosa. Results: compared with the matrix gel group, the number of neutrophils in CVL in N-9 gel group increased significantly (P 0.01), and the vaginal mucosal epithelium was abscission. Inflammatory cells increased, hemorrhage and edema increased significantly (P < 33.95 卤6.69), but there was no significant change in NFVR/ME-TISG group. Conclusion: NFVRR / ME-TISG does not cause inflammatory irritation in vaginal mucosa of miniature pigs, and the safety is good. It is expected to be further developed as a candidate for microbicides for external vaginal use.
【作者单位】：上海市计划生育科学研究所国家计划生育药具重点实验室;复旦大学公共卫生学院;上海交通大学农业与生物学院;
【基金】：国家重点研发计划资助项目(2016YFC1000905) 上海市科委项目(1514091200) 上海市环境卫生和劳动卫生学重点学科建设项目(15GWZK0201) 国家科技部中青年科技创新领军人才项目(万人计划)(新型外用避孕药和杀微生物剂的研究)
【分类号】：R965

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